Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Oropharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy
Authors: Irini Youssef, Jennifer Yoon, Nader Mohamed, Kaveh Zakeri, Robert H. Press, Linda Chen, Daphna Y. Gelblum, Sean M. McBride, Chiaojung Jillian Tsai, Nadeem Riaz, Yao Yu, Marc A. Cohen, Lara Ann Dunn, Alan L. Ho, Richard J. Wong, Loren S. Michel, Jay O. Boyle, Bhuvanesh Singh, Anuja Kriplani, Ian Ganly, Eric J. Sherman, David G. Pfister, James Fetten, Nancy Y. Lee
Journal: JAMA Network Open (2022)

Importance Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT. Objective To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy. Design, Setting, and Participants This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021. Exposures IMPT or IMRT with or without chemotherapy. Main Outcomes and Measures The main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ 2 tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups. Results The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16–positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16–positive disease. There were no significant differences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85% IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59). The incidence of acute toxic effects was significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P &amp;amp;lt; .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P &amp;amp;lt; .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P &amp;amp;lt; .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P &amp;amp;lt; .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P &amp;amp;lt; .001). There were no significant differences in chronic toxic effects except for xerostomia. Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months. Conclusions and Relevance In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.